Dietary Supplement Capsules Research Articles

A comparative metabolomics analysis of Açaí (Euterpe oleracea Mart.) fruit, food powder, and botanical dietary supplement extracts.

Euterpe oleracea Mart. (açaí) is a botanical of interest to many who seek functional foods that provide antioxidant and anti-inflammatory properties. Cancer patients are increasingly taking botanical dietary supplements containing açaí to complement their conventional therapeutics, which may lead to serious adverse events. Before testing our açaí extracts in vitro for botanical-drug interactions, the goal is to chemically characterize our extracts for compounds whose biological activity in açaí is unknown. The objective of this work was to develop a chemical fingerprinting method for untargeted characterization of açaí samples from a variety of sources, including food products and botanical dietary supplement capsules, made with multiple extraction solvents. An optimized LC-MS method was generated for in-depth untargeted fingerprinting of chemical constituents in açaí extracts. Statistical analysis models were used to describe relationships between the açaí extracts based on molecular features found in both positive and negative mode ESI. In an attempt to elucidate the differences in metabolites among açaí extracts from different cultivars, we identified or tentatively identified 173 metabolites from the 16 extracts made from 6 different sources. Of these compounds, there are 138 reported in açaí for the first time. Statistical models showed similar yet distinct differences between the extracts tested based on the polarity of compounds present and the origin of the source material. A high-resolution mass spectrometry method was generated that allowed us to greatly characterize 16 complex extracts made from different sources of açaí with different extraction solvent polarities.

Standardization of açaí extracts for in-vitro assays based on anthocyanin quantitation.

Euterpe oleracea Mart., commonly known as açaí, is a fruit that grows on a palm tree native to the Amazon region. Quantitation of bioactive constituents is a crucial preliminary step before utilizing extracts for biological assays so they may be normalized and administered according to a specific constituent concentration. Açaí has four main anthocyanin analytes: cyanidin 3-glucoside, cyanidin 3-sambubioside, cyanidin 3-rutinoside, and peonidin 3-rutinoside. This is the first comparison of açaí anthocyanin profiles between fresh fruits, processed powders, and botanical dietary supplement capsules. The materials examined shared a similar anthocyanin profile, with cyanidin 3-rutinoside being the most abundant (0.380 ± 0.006 - 15.1 ± 0.01 mg/g), followed by cyanidin 3-glucoside (0.0988 ± 0.0031 - 8.95 ± 0.01 mg/g). Among the botanical dietary supplement capsules, the two formulations varied greatly in anthocyanin concentration despite both being aqueous extracts (0.650 ± 0.011 - 0.924 ± 0.010 mg/g versus 1.23 ± 0.01 - 1.27 ± 0.02 mg/g). Previous LC-MS methods range from 35-120 min per injection, while we report a 10 min quantitative method for analysis of anthocyanins in various açaí materials that is fast, reproducible, and accurate. The method produced is useful to assure the quality, efficacy and safety of food and dietary supplement materials containing açaí.

Quantification of tocochromanols in vitamin E dietary supplements by instrumental thin-layer chromatography

A variety of vitamin E dietary supplement capsules (DSC) based on different natural oils or synthesis products are currently found on the market whose vitamin contents need to be controlled before and after marketing. Here, we present an instrumental thin-layer chromatography (TLC) method which allows a direct determination of all tocopherols (T) and tocotrienols (T3) as well as α-tocopherol acetate simultaneously in one run with short analysis time. For this purpose, contents of the DSC were extracted, applied on silica gel 60 plates, and developed with n-hexane/ethyl acetate/acetic acid, 90:10:2 (v/v/v) as mobile phase. The UV scan of the plate at 293 nm was used for quantification based on the peak height. Following the scan, the plate was treated with 10% sulphuric acid in methanol which led to characteristic yellow-to-brown colouring of the tocochromanol spots which allowed to distinguish tocochromanols from matrix components with similar Rf values. In most cases, determined vitamin E contents matched well with the information listed on the label of the investigated DSC samples. The method is fast, easy to perform and gently treats the analytes as it requires no thermal treatment prior to quantification, which makes it suitable as a screening method.

An Open-label Experience Trial to Evaluate the Effects of a Novel Supplement and Hair Serum Combination on Hair, Skin and Nails in Healthy Women

Abstract Objectives An open-label experience trial was conducted to evaluate the effects of LustrivaTM BH-002 on the health and appearance of women's hair, skin, and nails. LustrivaTM BH-002 is a two-step system that includes dietary supplement capsules (step 1) and a hair serum (step 2) that both contain novel, highly bioavailable sources of biotin (magnesium biotinate; MgBio) and silicon (inositol-stabilized arginine silicate; ASI). In preclinical studies, the Lustriva supplement improved the hair growth cycle, levels of collagen in the skin, and skin elasticity and texture. In a three month, double-blind, placebo-controlled trial in 90 women, Lustriva capsules increased hair thickness and reduced wrinkles compared to placebo. The following open-label study was conducted to evaluate the potential benefits of the LustrivaTM BH-002 two-step system. Methods Twelve (12) women were given a free supply of LustrivaTM BH-002 (capsules and hair serum) to use for 3 months. Each month, subjects received online survey questionnaires with questions focusing on hair, skin, and nail health. After completion of each survey questionnaire, subjects were compensated with a $25 gift card. Results The following results reflect participants' responses after using LustrivaTM BH-002 for three months. Hair surveys showed that 92% of women reported an improvement in overall hair volume, 82% of women reported an improvement in hair thickness, and 75% of women reported an improvement in hair shine. Nail surveys showed that 83% of women reported an improvement in nail strength and 83% of women reported an improvement in nail growth rate. Skin surveys showed that 75% of women reported an improvement in skin smoothness, 75% of women reported an improvement in overall skin health, 83% of women reported an improvement in how satisfied they were with how healthy their facial skin looked, and 83% of women were less bothered by how noticeable the lines on their face looked. Conclusions These data demonstrate that LustrivaTM BH-002, a two-step system that includes a dietary supplement and hair serum containing novel, highly absorbed biotin and silicon ingredients, improves various aspects of hair, skin, and nail health and appearance in women. Funding Sources This study was funded by JDS Therapeutics, LLC, the parent company of Bonafide®.

Quality control of dietary supplements: An economic green spectrofluorimetric assay of Raspberry ketone and its application to weight variation testing

Although Dietary supplements are readily accessible and extensively used worldwide, they are inadequately regulated and consumers are victims of manufacturers' fraud. Thus, quality regulations are required to ensure safety of products available to the public. We propose the first native spectrofluorimetric quality control assay of raspberry ketone, a popular dietary supplement ingredient for weight loss. This work relies on the constant wavelength synchronous scan of the Raspberry Ketone native fluorescence, overcoming the demerits of conventional excitation/ emission spectra. For the best measurement conditions, several parameters were optimized including Δλ value, diluting solvent, medium pH and the effect of surfactants/ macromolecules. In aqueous medium (Δλ = 110 nm), a linear relationship exists between synchronous fluorescence intensity at peak maximum 405.6 nm and solution concentration in the range 300–1500 ng/mL. Method sensitivity was recorded with LOD and LOQ values 60.63 and 183.72 ng/mL; respectively. Validation was done in accordance to International Conference on Harmonization (ICH) guidelines. This simple procedure was successfully applied to the analysis of Raspberry Ketone in commercially available dietary supplement capsules with average recovery 98.67% ± 1.74 and further extended to weight variation testing following the official United States Pharmacopeial (USP) guidelines. Finally, green assessment was done using the ''Analytical Eco-scale'' tool. The total score was 89/100 points revealing excellent greenness of our proposal. Our proposal is simple, eco-friendly and cheap. It can be conveniently adopted for routine quality control practices especially in developing countries.

Determination of sildenafil citrate adulterated in a dietary supplement capsule by LC/MS/MS

A liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was used to identify and quantify an adulterated substance, in a dietary supplement capsule. The capsule is claimed to be an extract of animal organs and traditional Chinese herbs and indicated for enhancing sexual activity. At first, the sample was extracted with 50% v/v methanol in water and the extract was injected directly into the LC/MS/MS with no separation and a full scan of positive ion eletrospray (ESI +) analysis was performed. The full scan mass spectrum was compared with the NLFD3/LM library created by Division 3rd of National Laboratories of Foods and Drugs for LC/MS/MS analysis. A sildenafil specific mass spectrum was matched indicating that the capsule may have been adulterated with sildenafil, the active ingredient of VIAGRA®. Furthermore, sildenafil was confirmed by carrying out a daughter ion scan and a parent ion scan. The daughter ion spectrum was compared with the NLFD3/LM library. A negative ion eletrospray (ESI -) analysis was performed for confirming the citrate salt in the capsule. The results indicated that the adulterated ingredient was sildenafil citrate. For quantitative analysis of the sildenafil citrate, multiple reaction monitoring (MRM) was performed. Pirenzepine 2HCL was used as the internal standard. A series of standards solution and sample solution with internal standard were analyzed by LC/ MS/MS. The analytical condition is as following: column: Cosmosil 5C18-AR, 4.6 x 150 mm; mobile phase:methanol:acetonitrile: 1% acetic acid (25:17:58); capillary voltage: 3 kV;cone voltage: 80 V; collision energy: 25 eV; source temperature: 120°C; desolvation temperature: 350°C. The detection limit was 40 ng/mL. An excellent calibration curve of sildenafil citrate was obtained with the γ 2 correlation coefficient of 0.9977. The RSDs of interday and intraday were between 7.56∼7.75% and 9.09∼11.25%, respectively. The analytical strategy and method is suitable for identification and measurement of sildenafil citrate adulterated in capsule. Amount of sildenafil citrate in the capsule was determined as 42.8 mg/capsule.

Effects of a novel nutraceutical combination (BruMeChol\u2122) in subjects with mild hypercholesterolemia: study protocol of a randomized, double-blind, controlled trial

BackgroundElevated cholesterol levels and systemic inflammation are considered relevant risk factors for cardiovascular disease (CVD) development and progression. Increasing evidence suggests that cholesterol-lowering and inflammation-lowering nutraceuticals are useful in the management of moderate hypercholesterolemia. Here, we describe the study protocol of a clinical trial aimed to evaluate the cholesterol and inflammatory lowering effect of an innovative dietary supplement (BruMeChol™, Mivell S.r.l., Italy), composed of a mixture of extracts of bergamot and olive fruits in association with vitamin K2 in subjects with mild hypercholesterolemia.MethodsThe study was planned as a randomized, double-blind, placebo-controlled, parallel group clinical trial for 12 weeks at the Cardiology Unit of the IRCCS INRCA of Ancona, Italy. A total of 125 subjects (age ≥ 40 years) with mild hypercholesterolemia (total serum cholesterol levels ≥ 200 and ≤ 250 mg/dl) will be recruited. Intervention arm participants will take one capsule of dietary supplement two times a day, 15 min before the main meal. Control arm participants will receive one capsule of placebo in the same way. The dietary supplement capsule contains the following ingredients: phytosterols, flavonoid-rich extract of bergamot fruit (Citrus bergamia), flavonoid-rich extract of olive fruit (Olea europaea), and vitamin K2. Participants will undergo a medical evaluation and chemical-clinical examinations, which include lipid profile, glycemia, biomarkers of renal, liver and cardiac/muscular functions, interleukins (IL 6, IL-32, IL-37, and IL-38), and innovative mediators of inflammation such as inflamma-miRs (miR-21 and miR-146a), at baseline, and after 6 and 12 weeks of treatment. The decrease in total cholesterol levels and inflammatory biomarkers will be the primary and secondary endpoints of the study.DiscussionThis protocol study, planned to verify the effects of BruMeChol™ dietary supplementation in subjects with mild hypercholesterolemia, could also contribute to new study designs for next large-scale multicenter clinical trials.Trial registrationAustralian New Zealand Clinical Trials Registry: ACTRN12619000170123. Retrospectively registered on 5 February 2019

Identification of two α-tocodienol isomers in palm oil after countercurrent chromatographic enrichment.

Countercurrent chromatography (CCC) was used for the enrichment of α-tocodienol (α-T2), a rare vitamin E-related minor compound previously tentatively detected in palm oil. Hitherto, only one isomer has been mentioned to occur at traces in palm oil. However, CCC fractionation followed by GC/MS measurements of all fractions resulted in the detection of two α-T2 isomers in five different palm oil vitamin E dietary supplement capsules. Five repetitive CCC separations of ~ 1g sample and additional purification steps by column chromatography provided ~ 2mg of two equally abundant α-T2 isomers with a purity of ~ 85%. The positions of the double bonds in the alkyl side chain could be assigned by means of two characteristic chemical shifts in the 1H NMR spectrum. Accordingly, the structures of the α-T2 isomers were 2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridec-3,11-dienyl)chroman-6-ol (double bonds in 3',11'-position) and 2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridec-7,11-dienyl)chroman-6-ol (double bonds in 7',11'-position). Natural occurrence of both isomers was proven by GC/MS screening of crude palm oil after saponification and CCC separation. Moreover, GC/MS analysis allowed the tentative assignment of γ-tocomonoenol (γ-T1) and β-tocomonoenol (β-T1) as trace compounds in palm oil.

Fast and Efficient RP-HPLC Method for Simultaneous Determination of Water-Soluble Vitamins in Some Nutraceutical Supplements

The purpose of this study is the development of analytical method for simultaneous determination of water-soluble vitamins (B1, B2, B3, B6, B9, B12 and vitamin C) in dietary supplement syrup, multivitamins and mineral dietary supplement syrup with iron, dietary supplement capsules and balanced supplemental nutrition for children by using gradient RP-HPLC methods with PDA detector. The separation of water-soluble vitamins was performed on waters Spherisorb ODS2 (250 mm×4.6mm, 5μm) column. The wavelength was 272 nm at room temperature and the detection limits ranged from 2.4 to 8.3 ng/µl. The average recovery was 98%-102 % and correlation coefficient (r) was 0.9992 to 1.

POTENTIAL EFFECTS OF SOME NATURAL DIETARY SUPPLEMENTS ON ANTHROPOMETRIC CHARACTERISTICS AMONGST WEIGHTLIFTER ATHLETES

This work was carried out to study the effect of using some natural dietary supplements; i.e. powders of date palm pits and pollen, ginseng roots, moringa leaves and royal jelly which giving orally in capsule to improve endurance of weightlifter athletes throughout 12 weeks in camp of sport Championship Sector belongs to the Armed Forces, Ministry of Defense, Future City, Cairo, Egypt. Collecting data showed that the suggested dietary supplement capsule had the highest value of the antioxidant activity (96.3%) and significant increases in total phenolic and flavonoids content (52.42 & 63.1 mg/g, respectively). Also, the anthropometric measurements showed a significant increase in weight and height in males compared to females. likewise, waist and mid upper arm circumference had significant increases in males compared to females, Male weightlifter athletes had significant muscles mass bigger than female one, and the fat mass for male was assessed as ‘‘Fitness’’ which ranged between (14 and 17%) but the female had fat mass that assessed as ‘‘Athletes’’ which ranged between (14 and 20%). The weights lifting by male and female increased during three months, and also revealed a significant increase in the efficiency of males in lifting weights higher than in the females during the period of 12 weeks. Thus, the results indicated that by incorporating natural dietary supplement powders in suggesting capsule, it is possible to enhance the performance of weightlifter athletes.

Monitoring of the Source of Gelatin in Dietary Supplement Capsules Sold on the Internet

상업적으로 유통되는 젤라틴 캡슐 제품은 소비자의 건강(예: 광우병) 및 종교적 신념에 대한 우려를 야기시킬 수 있다. 젤라틴은 대부분 소, 돼지 등에서 유래한 원료 물질을 가공한 것으로서, 가공 후 그 원료 물질을 분석하는 것은 대단히 어렵다. 따라서 정부 규제기관의 표시사항 준수여부 모니터링 연구가 주기적으로 필요하다. 본 연구에서는 인터넷에 유통되는 건강기능식품(n = 181)을 대상으로 젤라틴 캡슐의 원료 물질을 종 특이 PCR 방법으로 분석했다. 55개 제품의 경우 표시사항에 젤라틴 캡슐원료 물질에 대한 정보를 명시하였으나(예: bovine-, fish-and plant-derived gelatin), 126개 제품의 경우 사용 원료에 대한 정보 없이 “gelatin”으로 표시하였다. 이 126개 제품의 젤라틴 캡슐 분석 결과 51개 제품은 소 유래의 젤라틴을, 31개 제품은 돼지 유래의 젤라틴을, 그리고 44개 제품은 소와 돼지의 원료를 혼합하여 제작한 블렌딩 젤라틴을 사용한 것으로 밝혀졌다. 따라서 소비자의 알 권리, 종교적 신념 및 건강을 보호하기 위해 젤라틴 캡슐에 사용된 원료 물질을 표시사항에 제공하는 것은 매우 중요하다.

Extract-filter-shoot liquid chromatography with mass spectrometry for the analysis of vitamin D2 in a powdered supplement capsule and standard reference material 3280.

An "extract-filter-shoot" method for the analysis of vitamin D2, ergocalciferol, in a dry powdered dietary supplement capsule containing rice flour excipient and in a National Institute of Standards and Technology standard reference material 3280 is reported. Quantification of vitamin D2 was done by atmospheric pressure chemical ionization mass spectrometry using selected ion monitoring, two transitions of selected reaction monitoring, and extracted ion chromatograms from full scans. UV detection was used for the quantification of Vitamin D2 in the dry powder capsule, whereas interfering species rendered UV detection unreliable for standard reference material 3280. Average values for standard reference material 3280 ranged from 8.27 ± 0.58 to 8.33 ± 0.57 μg/g using internal standard calibration and response factor approaches, compared to the previous National Institute of Standards and Technology internal value for vitamin D2 of 8.78 ± 0.11 μg/g, and the recently updated reference value of 8.6 ± 2.6 μg/g. The powdered supplement capsule was found to contain 28.19 ± 0.35 to 28.67 ± 0.90 μg/capsule for a capsule labeled to contain 25.00 μg. The triacylglycerol composition of the rice flour excipient in the powdered supplement capsule determined by atmospheric pressure chemical ionization mass spectrometry is also reported.

Analysis of 5-hydroxytryptophan in the presence of excipients from dietary capsules: comparison between cyclic voltammetry and UV visible spectroscopy

5-Hydroxytryptophan (5-HTP) is an important neurochemical and is available as a dietary supplement, which is used to regulate eating behaviour and potentially overcome depression. Dietary supplements have undergone a change in their regulation, where improved analytical assessment is required during manufacturing. We compared cyclic voltammetry with UV visible spectroscopy for the detection of 5-HTP in capsules, where an emphasis was placed in understanding if recordings could be conducted in the presence of pharmaceutical excipients. Both voltammetric and spectroscopic methods had linear responses over a concentration range between 50 and 150 mg per 25 ml−1 of 5-HTP and similar limits of detection. There current response was increased for 5-HTP in the presence of magnesium stearate and silica, however in the presence of all capsule excipients there was no difference on the voltammetric response and current. Following oxidation of 5-HTP, electrode fouling was observed on the carbon composite electrodes. The electrode surface following fouling was partly regenerated following soaking in ethanol and fully recovered when the electrode was polished in alumina slurry for 5 s. Voltammetric responses were capable of detecting 5-HTP content within individual capsules with or without filtration of pharmaceutical excipients. Only following filtration was spectroscopy able to provide stable response of 5-HTP content within an individual capsule. Overall, voltammetric responses provide a means of conducting measurements of 5-HTP dietary supplement capsules without the need for extensive sample preparation, thus providing a total analysis time within 8 minutes.

‘Dilute‐and‐Shoot’ Method for Vitamin D Analysis in Dietary Supplement Capsules

Three methods are demonstrated for a complete analysis of vitamin D and triacylglycerols (TAGs) in fortified dietary supplements that virtually eliminates all chemical pretreatment prior to analysis. Three mass spectrometers, in parallel, plus a UV detector, an evaporative light scattering detector (ELSD), and a corona charged aerosol detector (CAD), were used simultaneously. The contents of gelcaps labeled as containing 1000 IU (25 mcg) vitamin D3 in safflower oil and 2000 IU (50 mcg) vitamin D3 in rice bran oil were analyzed without the need for lengthy saponification and extraction. Three to five gelcaps were analyzed using vitamin D2 as an internal standard. Vitamin D3 was analyzed using UV detection, selected ion monitoring (SIM) atmospheric pressure chemical ionization mass spectrometry (APCI‐MS), and two transitions of multiple reaction monitoring (MRM) APCI‐MS. TAGs in the oils were analyzed using full‐scan APCI‐MS, electrospray ionization (ESI) MS, up to MS4, plus two auxiliary detectors‐‐‐the ELSD and CAD. TAGs containing fatty acids up to 28 carbons in length were identified. The vitamin D contents of the gelcaps exceeded label values, and additional chromatographic peaks appeared when the source of vitamin D3 was fish oil (safflower oil gelcap) versus synthetic vitamin D3 (rice bran oil gelcap).

Reduction of common cold symptoms by encapsulated juice powder concentrate of fruits and vegetables: a randomised, double-blind, placebo-controlled trial

Dietary supplements have been suggested in the prevention of the common cold, but previous investigations have been inconsistent. The present study was designed to determine the preventive effect of a dietary supplement from fruits and vegetables on common cold symptoms. In a randomised, double-blind, placebo-controlled trial, healthcare professionals (mainly nursing staff aged 18–65 years) from a university hospital in Berlin, Germany, were randomised to four capsules of dietary supplement (Juice Plus+®) or matching placebo daily for 8 months, including a 2-month run-in period. The number of days with moderate or severe common cold symptoms within 6 months (primary outcome) was assessed by diary self-reports. We determined means and 95 % CI, and differences between the two groups were analysed by ANOVA. A total of 529 subjects were included into the primary analysis (Juice Plus+®: 263, placebo: 266). The mean age of the participants was 39·9 (sd 10·3) years, and 80 % of the participants were female. The mean number of days with moderate or severe common cold symptoms was 7·6 (95 % CI 6·5, 8·8) in the Juice Plus+® group and 9·5 (8·4, 10·6) in the placebo group (P = 0·023). The mean number of total days with any common cold symptoms was similar in the Juice Plus+® and in the placebo groups (29·4 (25·8, 33·0) v. 30·7 (27·1, 34·3), P = 0·616). Intake of a dietary supplement from fruits and vegetables was associated with a 20 % reduction of moderate or severe common cold symptom days in healthcare professionals particularly exposed to patient contact.

Attenuation of common cold symptoms by encapsulated juice powder concentrate

IntroductionDietary supplements have been suggested as preventive strategies for common cold, but previous results were inconsistent. This study aimed to assess the effect of a dietary supplement from fruits and vegetables on common cold symptoms in healthy healthcare professionals.MethodsThis was a randomized double‐blind placebo‐controlled trial. Subjects were taking four capsules of dietary supplement (Juice Plus+®) or matching placebo daily for eight months, including a two month run‐in period. We report means and 95% confidence intervals (CI) for the number of days with at least moderate common cold symptoms (primary endpoint) and number of days with any common cold symptoms. Differences between groups are analyzed with ANOVA.ResultsA total of 543 subjects were included, with 529 valid for primary analysis (intervention: 263, placebo: 266). The mean number of days with at least moderate common cold symptoms was 7.6 (95% CI 6.5–8.8) in the intervention and 9.5 (8.4–10.6) in the placebo group (P=0.023). The mean number of days with any common cold symptoms was 29.4 (25.8–33.0) in the intervention and 30.7 (27.1–34.3) in the placebo group (P=0.616).ConclusionIntake of a dietary supplement from fruits and vegetables was associated with a reduction of moderate or severe common cold symptoms, but not with a reduction of total days with common cold symptoms.Research support: NSA (TN, USA)

Premature ovarian failure and dehydroepiandrosterone

Since the first successful birth at our center following treatment with DHEA in a patient with premature ovarian failure (POF), all subsequent patients with POF underwent the same treatment protocol. Receiving very encouraging results (FSH level was decreased in the first five patients and all achieved pregnancy), it was decided to study the action of DHEA for a reasonable length of time and in a larger number of patients to confirm the effectiveness of this particular therapeutic regime.

Structure determination of new analogues of vardenafil and sildenafil in dietary supplements

New analogues of vardenafil and sildenafil illegally added to dietary supplements were detected by high-performance liquid chromatography (HPLC) analysis with a photodiode array detector (PDA). These compounds were isolated and their structures elucidated by mass spectrometry (MS), infrared (IR) spectroscopy, one- and two-dimensional nuclear magnetic resonance (NMR). One of the new analogues given the trivial name pseudovardenafil (compound 1) was structurally elucidated and shown to be 1-[[3-(1,4-dihydro-5-methyl-4-oxo-7-propylimidazo[5,1-f][1,2,4]triazin-2-yl)-4-ethoxyphenyl]sulfonyl]-piperidine. It was a vardenafil analogue isolated from a dietary supplement capsule. Compared with vardenafil, the piperidine ring was substituted for the ethylpiperazine group. The second new analogue, trivially named hydroxyhongdenafil (compound 2), was separated from bulk powder used as a raw material for a dietary supplement. The piperazine and phenyl groups were connected through an acetyl group instead of a sulfonyl group, and hydroxyethylpiperazine was substituted for the methylpiperazine of sildenafil. It was structurally elucidated as 5-[2-ethoxy-5-[[4-(2-hydroxyethyl)-1-piperazinyl]acetyl]phenyl]-1,4-dihydro-1-methyl-3-propyl-7H-pyrazolo[4,3-d]pyrimidin-7-one.

The US FDA has issued a nationwide alert warning consumers not to use Liqiang 4 Dietary Supplement Capsules

The US FDA has issued a nationwide alert warning consumers not to use Liqiang 4 Dietary Supplement Capsules

The US FDA has issued a nationwide alert warning consumers not to use Liqiang 4 Dietary Supplement Capsules

The US FDA has issued a nationwide alert warning consumers not to use Liqiang 4 Dietary Supplement Capsules